Process for preparing anti-cancer quinazoline compounds

• Main Authors: SANTAFIANOS, DINOS PAUL, LEHNER, RICHARD SHELTON, NORRIS, TIMOTHY
• Format: Patent
• Language: English
• Published: 31.01.2003
• Edition: 7
• Subjects: ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAININGELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN,SULFUR, SELENIUM OR TELLURIUM; AGRICULTURE; ANIMAL HUSBANDRY; APPARATUS THEREFOR; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES, AS HERBICIDES; CHEMISTRY; FERROUS OR NON-FERROUS ALLOYS; FISHING; FORESTRY; GENERAL METHODS OF ORGANIC CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HUNTING; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTSTHEREOF; PRETREATMENT OF RAW MATERIALS; PRODUCTION AND REFINING OF METALS; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS; TRAPPING; TREATMENT OF ALLOYS OR NON-FERROUS METALS

A compound of formula 9 is prepared by reacting a compound of formula 10 with a primary alcohol of the formula R7-OH in the presence of an alkali-metal or alkaline-metal hydroxide R7 is C1-C10 or -(C1-C6 alkyl)(C6-C10 aryl) optionally substituted by 1 to 3 substituents independently selected from halo, nitro, trifluoromethyl, trifluoromethoxy, alkylsulfonyl, alkyl, alkoxy, aryloxy and arylsulfonyl. In formula 9 and 10 R6 is alkyl or -(CH2)mO(CH2)nCH3 m is independently an integer from 1 to 6 and n is an integer from 0 to 3 R7 is -alkyl or -alkylaryl optionally substituted with 1-3 substituents independently selected from halo, nitro, trifluoromethyl, trifluoromethoxy, alkylsulfonyl, alkyl, alkoxy, aryloxy and arylsulfonyl. R8, R9 and R10 are each independently selected from H, alkyl, halo, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluoromethoxy, aziod, OR11, -C(O)R11, C(O)R11, -NR12C(O)OR14, -OC(O)R11, -NR12SO2R14, -SO2NR11R12, -NR12C(O)R11, -C(O)NR11R12, -NR11R12, -S(O)j(CH2)q(C6-C10 aryl), -NR12(CH2)q(C6-C10 aryl) and -(CH2)q(4-10 membered heterocyclic. The alkyl, aryl and heterocyclic groups can be optionally substituted by 1 to 5 substituents. R11 is independently selected from H, alkyl, -(CH2)q(C6-C10 aryl), and -(CH2)q(4-10 membered heterocyclic) and can be optionally substituted by 1 to 5 substituents. R12 is independently H or alkyl R15 is H, alkyl or -(CH2)q(C6-C10 aryl) q is an integer from 0 to 4 , and j is an integer from 0 to 2